Prior to the AD 1902 Plinian eruption of 8 km3 of dacite and subsequent growth of the >1 km3 Santiaguito dacite dome complex, Santa María volcano grew into an 8 km3 composite cone over ∼75 kyr in four phases (at 103–72, 72, 60–46, and 35–25 ka). The 1902 eruption occurred after an ∼25 kyr period of repose in growth of the composite cone. To provide context for processes that ultimately led to the 1902 eruption, we present geochemical and isotopic (Sr, Nd, Pb, U-series) data from lavas of the composite cone for which ages are constrained by 40Ar/39Ar dating. The four cone-building phases comprise basaltic to basaltic-andesite lava (51·4–56·1% SiO2) whose major- and trace-element compositions suggest that crystallization was important in differentiation. Relative to other Central American arc volcanoes, these lavas also have large 238U excesses and high 207Pb/204Pb ratios that imply melting of a mantle wedge modified to an unusual extent by fluid from subducted crust and sediment of the Cocos plate. Major- and trace-element and isotopic variations over time imply that mafic recharge and magma mixing were prevalent during early phases of cone-building, whereas assimilation processes were more dominant during the latest stage of cone growth. Indeed, some early erupted basalts have lower 143Nd/144Nd and higher 87Sr/86Sr ratios than more SiO2-rich basaltic andesites that erupted during the final phase of cone-building. These features point to an assimilant that is not typical continental crust and instead may be more like mid-ocean ridge basalt with respect to major- and trace-element composition and Sr, Nd, Pb, and U–Th isotope ratios. Energy-constrained modeling of a parental basalt that undergoes crystal fractionation, assimilation and periodic recharge with basalt in the lower crust can reproduce lava compositions erupted during phases I–III and the early part of phase IV. Modeling further indicates that assimilation within the lower crust of partially melted garnet-amphibolite metabasalt, without basaltic recharge, may produce the youngest cone-forming lavas in phase IV. These models link the 8 km3 of cone growth over 75 kyr to the mass flux of magma into the crust. Our findings suggest an along-arc magma flux into the lower crust beneath Santa María of >20 km3 km−1 Myr−1, which is higher than anticipated in recent numerical–thermal approaches to basalt–crust interaction. Consequently, the thermal incubation period needed to produce hybrid basaltic-andesite magma may be only a few tens of thousand years.